Placebo tablets po BID every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.

Efavirenz 600 mg qd every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.

Tenofovir/Emtricitabine 300/200 mg qd from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.

Other Names:

Stocrin

Truvada

Detailed Description:

This is a randomized, double blind, placebo-controlled, multicenter study testing the utility of a CCR5 antagonist (Maraviroc) as an adjuvant to a standard HAART regimen to decrease the incidence of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-infected patients naïve to antiretroviral treatment. The study duration will be 60 weeks, 276 subjects (138 per arm) will be recruited. The population included will be HIV-infected patients starting antiretroviral (ARV) therapy at the participating centers in Mexico and South Africa with a CD4 T cell count <100 cells/ul. Subjects will be randomized to receive either Maraviroc (study drug) or placebo in addition to background ARV therapy. The background antiretroviral regimen for all subjects will be: Efavirenz 600mg QD + Tenofovir 300 mg / Emtricitabine 200 mg QD; subjects will be randomized to one of the following arms: Arm A: background ARV + maraviroc 600mg po BID; Arm B: background ARV + placebo po BID. Patients will be followed for 48 weeks. The primary endpoint will be the occurrence of a defined IRIS event by week 24 of follow up. The success of the ARV therapy will also be evaluated by virologic and immunologic response at 24 and 48 weeks. Three immunology sub-studies are planned: 1) Sub-study A will be conformed by a subgroup of 40 subjects (20 from Mexico and 20 from South Africa), additional blood sampling will be performed to evaluate expression of immune activation markers; movement of central memory T cells into cell cycle and frequencies of expandable pathogen-reactive CD4+ and CD8+ T cells in circulation; 2) Sub-study B will be conformed by another subgroup of 60 subjects (all from South Africa), additional blood sampling will be performed to evaluate monocyte and CD4 T cell gene expression as related to activation-induced apoptosis and cytokine secretion.; 3) Sub-study C will evaluate the incidence of thromboembolic disease in the study patients along with baseline evaluation of possible bio-markers of pro-coagulant state.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection, as documented by any licensed rapid test kit and confirmed by Western blot or ELISA test kit at any time prior to study enrollment.

Plasma HIV-1 RNA is acceptable as an alternative confirmatory test.

Men and women age > 18 years.

Have not received any antiretroviral treatment before entering the study.

Patients who received Single dose nevirapine or any duration of AZT for PMTC will not be considered ARV naïve.

Patients with an opportunistic or HIV-related infection may be included according to the clinical judgment of the main investigator in each center when the patient is ready and able to start ARV therapy.

Creatinine clearance minor of 50* mL/min as estimated by the Cockcroft-Gault equation or Creatinine Clearance > 50ml/min as calculated by a formal creatinine clearance measurement

All women of reproductive potential (have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) must have a negative serum or urine b-HCG pregnancy test performed within 7 days before study entry.

Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (hysterectomy, oophorectomy, tubal ligation, or vasectomy) and azoospermia by patient-reported history is acceptable.

All subjects must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must agree to use a form of contraception as specified in the note below while receiving protocol-specified medication(s) and for one month after stopping the medication(s).

Ability and willingness of subject or legal guardian/representative to give written informed consent.

Use of the following drugs within 180 days prior to study entry: systemic cancer chemotherapy, systemic investigational agents, and immunomodulators (growth factors, immune globulin, interleukins, interferons).

Use of systemic corticosteroids in the last 2 weeks prior to randomization.

Decompensated liver disease (defined as stage C of Child-Pugh classification) at the beginning of the study.

An altered mental status that in the opinion of the investigator, will compromise the adherence to the protocol.

Allergy/sensitivity to study drug(s) or their formulations that cannot be substituted by another agent as described in section 5.1

Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

Serious illness that renders a subject unable to take the antiretroviral study regimen.

Serious medical illness that in the opinion of the investigator compromises the adherence and/or follow up of the protocol.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988780

Locations

United States, Maryland

NIH/NIAD

Bethesda, Maryland, United States, 20892

United States, Ohio

Center for AIDS Research. Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

HIV-1 Immunopathogenesis Laboratory. The Wistar Institute

Philadelphia, Pennsylvania, United States, 19104

Center for Clinical Epidemiology and Biostatistics. University of Pennsylvania School of Medicine